Elucidating interactions between behavior-generating circuits using functional and anatomical connectomics

 描述（由申请人提供）：大脑活动如何导致复杂和不稳定的行为输出，一直吸引着神经科学家和哲学家。越来越多的证据表明，复杂的行为是由大量简单（有时是竞争）回路的活动造成的。然而，即使是最简单的电路，我们的理解仍然参差不齐，部分原因是现有技术限制了研究人员一次只能研究电路的一个或几个方面。我们站在记录和成像技术革命的尖端，最终将使我们能够全面研究人类大脑的基本生物构建模块是如何构建和组装在一起的。即使是现在，上述限制也不再适用于某些不太复杂、更容易通过实验来实现的大脑。这些为理解我们复杂的大脑提供了有吸引力的垫脚石。欧洲药用水蛭相对简单的神经系统将被用来发展关于神经系统中所有细胞的活动如何共同产生重叠功能网络的个体行为的见解，这一现象-在更大的规模上，无疑增加了许多复杂性-对人类大脑功能也至关重要。将进行三种类型的实验：使用高分辨率电压敏感染料成像记录神经节中所有神经元的活动-这只动物大脑中的活动单位-因为它执行四种不同的行为-游泳，爬行，局部弯曲和缩短。使用电子显微镜重建完整的连接模式-“连接体”-相同的神经节成像。使用电生理学为解剖学连接体增加功能意义。获得神经节中所有单个神经元的同时活动记录，因为它产生了几种行为，这将是第一次。将这一记录与同一神经节的重建连接体相结合，将建立一个具有前所未有潜力的数据集，以促进我们对神经元连接与行为之间联系的理解。一个特别的重点将是跨越多个行为回路的神经元和突触连接，以确定它们在选择行为中的作用。该项目将产生大量关于电路解剖和神经元活动的数据。这些数据将普遍提供，以便其他实验室可以生成和测试他们自己的关于水蛭神经回路功能和连接性的假设。水蛭神经系统用来选择和执行行为的动力学的许多方面似乎与更复杂的大脑所使用的机制相似。因此，我们和其他使用我们数据的用户所产生的假设的价值可能会远远超出水蛭，延伸到包括我们自己在内的分类树的遥远分支。

 DESCRIPTION (provided by applicant): How brain activity can lead to complex and flexible behavioral outputs has fascinated neuroscientists and philosophers alike. There is mounting evidence that complex behaviors result from the activity of a multitude of simpler (sometimes competing) circuits. Yet, our understanding of even the simplest circuits remains spotty, in part because available technology has limited researchers to studying only one or a few aspects of a circuit at a time. We stand at the cusp of a revolution in recording and imaging technology that will ultimately allow us to investigate comprehensively how the fundamental biological building blocks of the human brain are constructed and fit together. Even now, the limitations mentioned no longer apply to certain less complex, more experimentally approachable brains. These provide attractive stepping stones for understanding our own complex brain. The relatively simple nervous system of the European medicinal leech will be used to develop insights about how the activity of all the cells in a nervous system together produce individual behaviors from overlapping functional networks, a phenomenon that - at a much larger scale and undoubtedly with many complexities added - is also crucial to human brain function. Three types of experiments will be performed: Record the activity of all the neurons in a ganglion - the unit of activity in this animal's brain - using high-resolution voltage-sensitive dye imaging, as it perfors four different behaviors - swimming, crawling, local bending, and shortening. Use electron microscopy to reconstruct the full connectivity pattern - the "connectome" - of the same ganglion that was imaged. Use electrophysiology to add functional significance to the anatomical connectome. Obtaining a simultaneous activity record of all the individual neurons in a ganglion as it generates several behaviors will be a first. Combining this record with the reconstructed connectome of that very same ganglion will establish a data set with unprecedented potential for advancing our understanding of the link between neuronal connectivity and behavior. A particular focus will be on neurons and synaptic connections that span multiple behavioral circuits, to determine their roles in selecting behaviors. This project will generate huge amounts of data on circuit anatomy and neuronal activity. These data will be made generally available, so that other laboratories can generate and test hypotheses of their own on function and connectivity of leech neural circuits. Many aspects of the dynamics that the leech nervous system uses to select and perform behaviors appear to be similar to the mechanisms used by more complex brains. Accordingly, the value of the hypotheses that we and other users of our data will generate may extend far beyond the leech to distant branches of the taxonomic tree including our own.